Sodium Hydroxide → 2-(1-{[(S)-Cyclopropyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-2-oxo-propyl)-6-fluoro-benzoic acid

HRID 1962390

Reaktionsgleichung

Reaktionsgleichung von HRID 1962390
[C:1]([C:4]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([F:14])[C:8]=2[C:7](=[O:15])[O:6][C:5]=1[NH:16][C@@H:17]([CH:25]1[CH2:27][CH2:26]1)[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=1)(=[O:3])[CH3:2].[OH-:28].[Na+]>O1CCCC1.CO>[CH:25]1([C@H:17]([NH:16][C:5]([CH:4]([C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([F:14])[C:8]=2[C:7]([OH:6])=[O:15])[C:1](=[O:3])[CH3:2])=[O:28])[C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[CH2:27][CH2:26]1

Komponenten

5

Edukt 2

HCID 14798Sodium HydroxideHCID 577332754-Acetyl-3-{[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amino}-8-fluoro-isochromen-1-one

Produkt 1

HCID 577332502-(1-{[(S)-Cyclopropyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-2-oxo-propyl)-6-fluoro-benzoic acidAusbeute 97,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

4-Acetyl-3-{[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amino}-8-fluoro-2-benzopyran-1-one (14.30 g, 38.72 mmol) was dissolved in a mixture of tetrahydrofuran (50 mL) and methanol (50 mL) and placed on an ice/water bath with stirring. NaOH (1 M in H2O, 100 ml) was added and stirring continued for 1 hour. The cold bath removed and the mixture was allowed to warm to r.t. (20° C.) during 1 hour. The reaction mixture was poured into ice-water mixture (200 g+200 ml), followed by slow addition of 2 M aq. HCl (200 mL) and extracted with ethyl acetate (200 mL), washed with sat. aq. NaCl, dried (Na2SO4), filtered and evaporated to give the title compound (14.65 g, yield 97.7%) as a pale brown foam. The crude product was used in the next step without further purification. LC-MS (m/z) 388.3 (MH+); tR=1.2. 1H NMR (500 MHz, DMSO-d6): a mixture of tautomers and diastereoisomers.

Aufarbeitung

  1. customplaced on an ice/water bath
  2. stirringstirring
  3. customThe cold bath removed
  4. additionThe reaction mixture was poured into ice-water mixture (200 g+200 ml)
  5. additionfollowed by slow addition of 2 M aq. HCl (200 mL)
  6. extractionextracted with ethyl acetate (200 mL)
  7. washwashed with sat. aq. NaCl
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-643e204d975b4a37aa0aa417afef7cb0
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415356B2

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